The risk of developing colonic neoplasia may be determined by the combination of inherited susceptibility and environmental factors. This research proposal is designed to examine the main effects and interactions between genetic susceptibility factors, dietary factors, and nutritional biochemical measures on the risk of colorectal adenomas. The ultimate goal is to define genetic susceptibility factors and nutritional biochemical markers that can be used to identify a population at high risk for developing colorectal neoplasia in which to focus preventive interventions. The study will be conducted using data on risk factors for colorectal adenomas and stored serum and DNA collected at baseline from participants in the VA Cooperative Study #380. Risk factor data will be obtained from a questionnaire completed by participants at baseline containing information on family history, physical activity, obesity, tobacco, alcohol, NSAIDs, dietary intake of fat, fiber, fruits and vegetables, and calcium. DNA will be harvested and analyzed for potential genetic susceptibility factors (apolipoprotein E, NAD(P)H:quinone oxidoreductase, and glutathione-S-transferase mu genotypes). Dietary intake data from a good frequency questionnaire will be analyzed. Nutritional biochemical measures (ferritin, selenium, and cholesterol) will be analyzed from the stored blood serum. The main and interacting effects of these measures on the risk of colorectal adenomas will be analyzed in 600 cases of adenomas and 300 controls frequency matched on age, gender, and ethnicity.